An Epithelial-Mesenchymal Gene Regulatory Network that Controls Tooth Organogenesis

Many vertebrate organs form via the sequential, reciprocal exchange of signaling molecules between juxtaposed epithelial (E) and mesenchymal (M) tissues. For example, the instructive signaling potential for tooth development (odontogenesis) resides in the dental epithelium at the initiation-stage, and subsequently shifts to the dental mesenchyme one day later at the bud-stage. However, the properties of the gene regulatory networks (GRNs) that control the signaling dynamics during epithelial-mesenchymal (E-M) interactions in organogenesis are largely unknown. This dissertation describes an interdisciplinary effort between developmental and systems biology to elucidate the E-M GRN that controls early odontogenesis. The results provide a molecular mechanism for the longstanding paradigm of sequential, reciprocal E-M tissue interactions in development.